During the cell cycle, growth in size and cell DNA replication are coordinated. However, recent evidence has shown that the two processes can be dissociated and are under different control mechanisms. Preliminary work suggests that the p53 protein, which plays a role in the proliferation of mammalian cells, may also regulate the amount of total cellular RNA. We propose to investigate the role of the p53 protein in growth in size and cell DNA replication by using the system of mitogen-stimulated lymphocytes. This system is based on the observation that T-lymphocytes grow in size but do not enter S phase when exposed to phytohemagglutin, but do enter S phase when macrophages (or Interleukin-2) are added to the phytohemagglutinin stimulated populations. By using this system, a monoclonal antibody against the p53 protein, a cDNA probe of p53 mRNA, and microinjection, we intend to further define the role of the p53 protein in cell proliferation. In turn, these studies should establish a better basis for future investigations dealing with the mechanism by which the p53 protein regulates the progression of cells through the cell cycle.